We have demonstrated the feasibility of prolonged (10 week) pancreas organ culture and growth in vitro in a defined medium. In addition we have determined that certain known carcinogens in this system produce alterations in morphology and growth. It is the purpose of this project: to determine whether the observed changes are neoplastic and if so, this should be an ideal system to study pancreas carcinogenesis. Following dimethylnitrosourea (DMNU) or dimethylnitrosamine (DMN) administration, ultrastructural alteration (EM), cell proliferation (DNA synthesis, autoradiographic) and enzymatic activity (i.e.: amylase, lipase, chymotropsin, etc.) will be studied. Morphologically transformed explants will be implanted in vivo to evaluate their biological transformation. In earlier work it was established that a relative methyl deficiency in organ culture allowed pancreatic growth but prevented differentiation. The separation of these two processes (proliferation and differentiation) will allow study of the actions of carcinogens under conditions of embryonic growth.